Abstract

Author summary Studying how to safely expand stem cells in culture is essential for regenerative medicine applications. Hence there is a clear need to decode how the cell cycle of mouse embryonic stem cells (mESCs) is regulated. Tcf3 and Tcf1 belong to the Tcf family of proteins. Tcf/Lef are effectors of the Wnt/β-catenin pathway and Tcf3 controls mESC pluripotency. Here we identified a recruitment site for Tcf1 embedded into a number of cell cycle repressor genes such as p15Ink4b, p16Ink4a and p19Arf. Tcf1-mediated activation of these genes drastically slows down proliferation of mESCs. In conclusion, here we showed that the Wnt pathway, besides controlling mESC pluripotency via Tcf3, also regulates mESC cell cycle through the recruitment of Tcf1 to the regulatory sites of key cell cycle genes.

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